Purpose: The purpose of this study was to ascertain whether radiation adaptive response could be induced by high dose I-131 therapy in patients with differentiated thyroid cancer. Materials and Methods: Lymphocytes from 21 patients (7 males, 14 females, mean age 55¡¾12 years) were collected before and after administration of 5,550 MBq (150 mCi) I-131. They were exposed to a challenge dose of 1 Gy gamma rays using a Cs-137 cell irradiator. The number of ring-form (R) and dicentric (D) chromosomes was counted under the light microscope, and used to calculate the frequency of chromosomal aberration. Ydr, which was defined as the sum of R and D divided by the total number of counted lymphocytes. Results: Ydr in patients before I-131 therapy (0.09¡¾0.01) was not different from that of controls (0.08¡¾0.01). Ydr was significantly increased to 0.13¡¾0.02 (p<0.0001) after I-131 therapy. Increase of Ydr after the challenge irradiation of 1 Gy was significantly lower in patients after I-131 therapy than before I-131 therapy (0.17¡¾0.03 vs 0.21¡¾0.02, p<0.0001). Cycloheximide (CHM), an inhibitor of protein synthesis, abolished this effect. Ydr after CHM (0.20¡¾0.01) was significantly higher than Ydr after I-131 therapy (0.17¡¾0.03, p<0.0001), but was not different from Ydr before I-131 therapy (0.21¡¾0.02). Conclusion: High dose I-131 therapy induces an adaptive response in peripheral lymphocytes of patients with well-differentiated thyroid cancer, which is associated with protein synthesis. (Korean J Nucl Med 2001;35:83-88)